The fully reduced (10 to the -2 M dithiothreitol) and dissociated (6 M Guanidine HCl) subunits of C3 and C5 have been isolated by gel filtration (450 x 2.5 cm., 4% beaded agrose bed). Immunizations of rabbits have yielded monospecific antisera directed toward C3 alpha, C3 beta and C5 beta. Anti-subunit antisera show limited to no reactivity with the native homologous parent protein. Anti-native C3 or C5 antisera do not react with isolated subunits. Anti-subunit antisera and, to a limited extent, also anti-native C3-C5 antisera react with denatured unreduced parent protein. The nature of the denaturating process which leads to the antigenic modification of C3 and C5 is currently being studied, as well as the possibility that similar antigenic modifications may occur naturally in the complement reaction. BIBLIOGRAPHIC REFERENCES: Nilsson, U.R. and Wyman, S.: Interaction of Anionic Detergents with Human C3 and Consequent Alteration of C3 Antigenicity. J. Immunol. 116: 1744, 1976 (Abstract). Nilsson, U.R. and Wyman, S.: Antigenicity of Detergent Treated Human C3. Fed. Proc. 35: 357, 1976 (Abstract).